rs150072792

Variant names:

• chr1-151342349-G-A
• rs150072792
• NM_001025603.2:c.1688C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-151342349-G-A
• chr1-151342349-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001025603.2(RFX5):​c.1688C>T​(p.Ser563Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000548 in 1,614,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (0 hom.)
• Consequence: RFX5 NM_001025603.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:5
• Conservation: PhyloP100: 2.33
• Publications: 3 publications found

Genes affected

RFX5 (HGNC:9986): (regulatory factor X5) A lack of MHC-II expression results in a severe immunodeficiency syndrome called MHC-II deficiency, or the bare lymphocyte syndrome (BLS; MIM 209920). At least 4 complementation groups have been identified in B-cell lines established from patients with BLS. The molecular defects in complementation groups B, C, and D all lead to a deficiency in RFX, a nuclear protein complex that binds to the X box of MHC-II promoters. The lack of RFX binding activity in complementation group C results from mutations in the RFX5 gene encoding the 75-kD subunit of RFX (Steimle et al., 1995). RFX5 is the fifth member of the growing family of DNA-binding proteins sharing a novel and highly characteristic DNA-binding domain called the RFX motif. Multiple alternatively spliced transcript variants have been found but the full-length natures of only two have been determined. [provided by RefSeq, Jul 2008]

RFX5-AS1 (HGNC:40503): (RFX5 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015573829).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025603.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFX5	NM_001025603.2	MANE Select	c.1688C>T	p.Ser563Leu	missense	Exon 11 of 11	NP_001020774.1	P48382-1
	RFX5	NM_000449.4		c.1688C>T	p.Ser563Leu	missense	Exon 11 of 11	NP_000440.1	P48382-1
	RFX5	NM_001379412.1		c.1688C>T	p.Ser563Leu	missense	Exon 11 of 11	NP_001366341.1	P48382-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFX5	ENST00000452671.7	TSL:1 MANE Select	c.1688C>T	p.Ser563Leu	missense	Exon 11 of 11	ENSP00000389130.2	P48382-1
	RFX5	ENST00000290524.8	TSL:1	c.1688C>T	p.Ser563Leu	missense	Exon 11 of 11	ENSP00000290524.4	P48382-1
	RFX5	ENST00000368870.6	TSL:5	c.1688C>T	p.Ser563Leu	missense	Exon 11 of 11	ENSP00000357864.2	P48382-1

Frequencies

GnomAD3 genomes AF: 0.000493 AC: 75 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000577 AC: 145 AN: 251488 AF XY: 0.000493

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00129

Gnomad NFE exome AF: 0.000483

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.000553 AC: 809 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.000547 AC XY: 398 AN XY: 727248

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.00123 AC: 55 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00146 AC: 78 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.000573 AC: 637 AN: 1112012

Other (OTH) AF: 0.000447 AC: 27 AN: 60396

GnomAD4 genome AF: 0.000493 AC: 75 AN: 152276 Hom.: 0 Cov.: 32 AF XY: 0.000484 AC XY: 36 AN XY: 74454

African (AFR) AF: 0.000168 AC: 7 AN: 41566

American (AMR) AF: 0.000392 AC: 6 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.000566 AC: 6 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000667 Hom.: 0

Bravo AF: 0.000465

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000469 AC: 57

EpiCase AF: 0.000273

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	4	-	MHC class II deficiency (4)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.099	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.3
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.023
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.047	D
Polyphen		0.32	B
Vest4		0.059
MVP		0.50
MPC		0.12
ClinPred		0.030	T
GERP RS		4.2
Varity_R		0.063
gMVP		0.13
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs150072792; hg19: chr1-151314825; COSMIC: COSV51837834; COSMIC: COSV51837834;